Growth hormone (GH) is a pituitary-derived protein that stimulates somatic growth and other anabolic processes. Recombinant human GH is used to stimulate linear growth in children and to treat cachexia in AIDS patients. The protein must be injected daily for maximum effectiveness. We propose to create modified GH proteins that are equal or superior to natural GH in stimulating anabolic processes in vivo, but which require less frequent dosing, on the order of once per week or once every other week. During Phase I we identified sites in GH that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will manufacture sufficient quantities of the modified GH proteins for testing in animal models of GH deficiency and cachexia. The improved in vivo characteristics of the novel GH proteins may reduce the amount of GH required per patient, improve patient quality of life and result in considerable cost savings to patients and healthcare providers. GH is a prototype for a large family of structurally related cytokines and growth factors. Results obtained from these studies will be valuable for creating long-acting visions of other members of the GH supergene family for use in treating cancer, infectious diseases and hematopoietic disorder. PROPOSED COMMERCIAL APPLICATION: GH is used to stimulate linear growth in children of short stature and to treat cachexia in AIDS patients. Worldwide sales of GH were $1.4 billion in 1997. The long-acting GH proteins under development will improve drug efficacy and reduce the number of injections required per patient from once per day to once per week or once ever other week. The need for less frequent injections will result in significant cost savings and improve patient compliance and quality of life.